Inhibitors of the C(2)-symmetric HIV-1 protease: nonsymmetric binding of a symmetric cyclic sulfamide with ketoxime groups in the P2/P2' side chains.

Hultén, J; Andersson, H O; Schaal, W; Danielson, H U; Classon, B; Kvarnström, I; Karlén, A; Unge, T; Samuelsson, B; Hallberg, A

Hultén, J; Andersson, H O; Schaal, W; Danielson, H U; Classon, B; Kvarnström, I; Karlén, A; Unge, T; Samuelsson, B; Hallberg, A.

Afiliación

Hultén J; Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.

J Med Chem ; 42(20): 4054-61, 1999 Oct 07.

Article en En | MEDLINE | ID: mdl-10514275

RESUMEN

Symmetric cyclic sulfamides, substituted in the P2/P2' position with functional groups foreseen to bind preferentially to the S2/S2' subsites of HIV-1 protease, have been prepared. Despite efforts to promote a symmetric binding, the sulfamides seemed prone to bind nonsymmetrically, as deduced from X-ray crystal structure analysis of one of the most potent inhibitors, possessing ketoxime groups in the P2/P2' side chains. Ab initio calculations suggested that the nonsymmetric conformation of the cyclic sulfamide scaffold had lower energy than the corresponding symmetric, cyclic urea-like conformation.

Asunto(s)

Inhibidores de la Proteasa del VIH/química; Proteasa del VIH/química; Sulfonamidas/química; Cristalografía por Rayos X; Modelos Moleculares; Conformación Molecular; Compuestos de Fenilurea/química; Espectrometría de Fluorescencia

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfonamidas / Proteasa del VIH / Inhibidores de la Proteasa del VIH Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 1999 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos

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